Studies to investigate the regulation of hepatic cholesterol ester metabolism have been begun. The primary focus is on the enzyme acyl coenzyme A cholesterol-O acyltransferase. To date a number of circumstances which alter the activity of this enzyme in vivo have been found. These include cholesterol feeding, Triton WR 1339 administration, and mevalonate administration. A general theory has been proposed to explain the mechanism by which the enzyme is regulated and studies are proposed to validate it. In addition, the subcellular localization of the enzyme will be studied and attempts to solubilize and purify the enzyme will be continued. Finally, experiments designed to determine the contribution that hepatic cholesterol esters make to the circulating cholesterol ester pool will be evaluated.